A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

被引：183

作者：

Zhu, Pengpeng ^{[1
]}

He, Fang ^{[2
]}

Hou, Yixuan ^{[3
]}

Tu, Gang ^{[4
]}

Li, Qiao ^{[1
]}

Jin, Ting ^{[1
]}

Zeng, Huan ^{[1
]}

Qin, Yilu ^{[1
]}

Wan, Xueying ^{[1
]}

Qiao, Yina ^{[1
]}

Qiu, Yuxiang ^{[1
]}

Teng, Yong ^{[5
,6
]}

Liu, Manran ^{[1
]}

机构：

[1] Chongqing Med Univ, Key Lab Lab Med Diagnost, Chinese Minist Educ, Chongqing 400016, Peoples R China

[2] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing 400016, Peoples R China

[3] Chongqing Med Univ, Expt Teaching Ctr Basic Med Sci, Chongqing 400016, Peoples R China

[4] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing 400016, Peoples R China

[5] Dent Coll Georgia, Dept Oral Biol & Dx Sci, Augusta, GA 30907 USA

[6] Augusta Univ, Georgia Canc Ctr, Augusta, GA 30907 USA

来源：

ONCOGENE | 2021年 / 40卷 / 09期

基金：

中国国家自然科学基金;

关键词：

LNCRNA THOR INCREASES; TUMOR HYPOXIA; PROLIFERATION; METASTASIS; HIF-1-ALPHA; EXPRESSION; BINDING; RECOGNITION; INVASION; FEEDBACK;

D O I：

10.1038/s41388-020-01638-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

引用

页码：1609 / 1627

页数：19

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